title: Metabolic flux is a determinant of the evolutionary rates of enzyme-encoding genes.
abstract: Relationships between evolutionary rates and gene properties on a genomic, functional, pathway, or system level are being explored to unravel the principles of the evolutionary process. In particular, functional network properties have been analyzed to recognize the constraints they may impose on the evolutionary fate of genes. Here we took as a case study the core metabolic network in human erythrocytes and we analyzed the relationship between the evolutionary rates of its genes and the metabolic flux distribution throughout it. We found that metabolic flux correlates with the ratio of nonsynonymous to synonymous substitution rates. Genes encoding enzymes that carry high fluxes have been more constrained in their evolution, while purifying selection is more relaxed in genes encoding enzymes carrying low metabolic fluxes. These results demonstrate the importance of considering the dynamical functioning of gene networks when assessing the action of selection on system-level properties.
authors.affiliation: Institute of Evolutionary Biology (CSIC- Pompeu Fabra University), CEXS-UPF-PRBB, Dr. Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Martino
authors.initials: M
authors.lastname: Colombo
authors.forename: Hafid
authors.initials: H
authors.lastname: Laayouni
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Invergo
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
authors.forename: Ludovica
authors.initials: L
authors.lastname: Montanucci
mesh_terms: D000818:Animals; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D011323:Primates; D012641:Selection, Genetic
chemical_list: D004798:Enzymes
keywords: Enzyme evolution; erythrocyte metabolic network; molecular evolution; network dynamics; selective pressures